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evidence to suggest that the use of AHAs to provide additional therapy may be effective for improving some patient and organisational outcomes. Review registration CRD42019127449.Background Over the past 30 years, the healthcare industry has increasingly turned its attention to rare diseases. Regulators have emphasized the need for clinical research in this area to be patient-centered. However, there is a lack of evidence concerning whether this need is actually met. In this paper, we aim to address this gap. Methods First, we describe the state of patient-centricity in clinical research in rare diseases based on a targeted literature review. Second, we discuss recommendations from scientific bodies on patient-reported outcome (PRO) measures in rare diseases. Third, we analyze data collected from EMA's and FDA's websites concerning rare disease labeling claims and data from Clinicaltrials.gov concerning the use of PRO measures in rare disease pivotal trials. Fourth, we perform an exhaustive literature review on the use of PRO measures in the pharmaceutical industry, including all phases of clinical research, observational/registry studies, and instrument development and validation. Retoo few measures for the multitude of rare diseases. We call for a clear guidance on patient engagement and suggest a realistic approach to the adaptation of PRO strategy to the specific context of clinical research in rare diseases.Background Parameters that mark the timing of left ventricular (LV) reverse remodeling following transcatheter aortic valve replacement (TAVR) are incompletely defined. This study aims to identify the dynamics of LV strain derived from speckle tracking echocardiography in a cohort of patients with severe aortic stenosis (AS) who underwent TAVR and its correlation with postprocedural outcomes. Methods We selected 150 consecutive patients (82 ± 4 years old, STS score 6.4 ± 6.2) who underwent transfemoral TAVR between 07/2016 and 12/2017 at our tertiary care center. All patients were evaluated at baseline, 1 week after TAVR, and 3 months following TAVR. Results The global longitudinal strain (GLS) 1 week following TAVR was comparable to that at baseline (- 15,9 ± 4.3 vs - 16.8 ± 4.1; p = NS) but significantly improved at 3 months following TAVR (- 15.9 ± 4.3% vs. -19.5 ± 3.5%; p less then 0.001). No significant changes in global circumferential strain (GCS) and global radial strain (GRS) were detectable. The ejection fraction was significantly improved 1 week after the TAVR procedure. The baseline GLS correlated directly with the complication rate (R = 0.36, p = 0.005). The linear regression analysis showed that the main predictors of the improvement in the GLS at 3 months in our cohort were baseline GRS and GCS. Conclusion GLS improves at 3 months after TAVR, while LV ejection fraction does not show a substantial change, signaling an early recovery of LV longitudinal function after the intervention. Additionally, GLS has a direct correlation with the postprocedural outcomes. GLS improvement might emerge as a valuable parameter for a tailored follow-up in TAVR patients.Introduction In the work-up strategy for pulmonary embolism (PE) in the ED, the recently introduced YEARS rule allows the raising of the D-dimer threshold to 1000 ng/ml in patients with no signs of deep venous thrombosis and no hemoptysis and in whom PE is not the most likely diagnosis. However, this decision rule has never been prospectively compared to the usual strategy. Furthermore, it is unclear if the YEARS rule can be used on top of the Pulmonary Embolism Rule-out Criteria (PERC). We aim to assess the non-inferiority of YEARS compared to current guidelines to rule out PE among PERC-positive ED patients with suspicion of PE. Methods/design The MODIGLIANI study is a multicenter, European, non-inferiority, cluster-randomized, two periods cross-over, controlled trial. Each center will be randomized for the sequence of two 4-month periods intervention (MOdified Diagnostic Strategy MODS) followed by control (usual care), or control followed by intervention with 1 month of "wash-out" between the two periods. In the control period, the threshold will be as usual (500 ng/ml for patients aged 50 years or younger and age × 10 for older patients). In the MODS period, the threshold of D-dimers to rule out PE will be raised to 1000 ng/ml if no item of the YEARS score is present or will remain unchanged otherwise. Patients will be included if they have a suspicion of PE, defined as chest pain, dyspnea, or syncope. Non-inclusion criteria comprise a high clinical probability of PE or PERC-negative patients with low clinical probability. Ethics and dissemination The study has received the following approvals Comité de protection des personnes Ile de France XI (France) and Comité de Ética de la Investigación con medicamentos del Hospital Clínic de Barcelona (Spain). Results will be made available to all included participants and other researchers. Trial registration ClinicalTrials.gov, NCT04032769. Registered on 24 July 2019.Background This study aims to establish a multi-agent system model to provide accurate suggestions for the policy proposal of controlling the unreasonable growth of medical expenses charged by public hospitals in China. Methods A multi-agent system model was employed in this study. Agents of this model were divided into patients, doctors, medical institutions, the government, and medical insurance agencies. The model was composed of two subsystems the disease and medical-seeking subsystem, and the medical expenses subsystem. Policy intervention experiments were conducted on patients' medical-seeking preferences, doctors' public welfare behaviors, and the government's financial investment. Results At present, medical expenses in China are unreasonable and keep increasing, and the proportion of medicine and physical examination expenses to total medical expenses for public hospitals is unreasonable. Intervention experiments suggested that expanding the promotion and application of the community first-visit syst, response speed, and implementation cost of policies as well.Background Behçet's disease (BD) is a chronic multisystemic vasculitis that may emerge with musculoskeletal system involvements, oral-genital recurrent aphthae, mucocutaneous lesions, and ocular symptoms. Arthritis in BD is usually non-erosive and not related to crippling disease. Erosive arthropathy is a very rare manifestation of BD. Case presentation Herein, we present a 60-year-old male patient suffering from BD for 33 years with erosive arthritis in his second metacarpophalangeal joint. After we assessed his finger by X-ray, we diagnosed erosive arthropathy quickly by musculoskeletal ultrasonography. In addition, a systematic literature search was performed via the PubMed and Scopus databases using the keywords, 'Behçet's disease [AND] erosive/destructive arthritis'. Conclusions Erosive arthritis due to BD can be evaluated by ultrasonography in an easy, fast and cost-effective manner. The literature search between 1985 and December 2019 revealed a total of 19 patients with peripheral erosive arthropathy related to BD and the characteristics of the results are summarized in the paper.Here, we report a unique acute myeloid leukemia (AML) bone marrow-derived mesenchymal stem cell (MSC) with both mesenchymal and endothelial potential, which we have named Mesenchymal Cancer Stem Cells (MCSCs). These MCSCs are CD90-CD13-CD44+ and differ from MSCs in isolation, expansion, differentiation, immunophenotype, and cytokine release profile. Furthermore, blocking CD44 inhibited the proliferation and cluster formation of early MCSCs with lower ICAM-1 protein levels. Similar CD90-CD44+ cancer stem cells have been reported in both gastric and breast cancers, which grew in floating spheres in vitro and exhibited mesenchymal features and high metastatic/tumorigenic capabilities in vivo. Our novel discovery provides the first evidence that certain AMLs may be comprised of both hematopoietic and stromal malignant cells. Targeting MCSCs and their cytokine release has potential as a novel therapeutic approach in AML.Background The aim of this study was to investigate the amount and sources of stress in dental undergraduate students in Fujian, China, and the factors associated with stress. Methods This cross-sectional study was conducted during the second semester of the 2017-2018 academic year at the School of Stomatology, Fujian Medical University, China. A total of 396 students were surveyed with the Dental Environment Stress Questionnaire (DES) and the Perceived Stress Scale (PSS) using an online survey system. The participants' demographic information, including sex, age, year of study, and grade point average (GPA) was also collected. One-way analysis of variance (ANOVA) was performed to compare the stress scores. AZD3514 molecular weight Pearson correlation and multiple linear regression analyses were conducted to explore the associated factors of stress and academic performance. All statistical analyses were performed at a significance level of 5%. Results A total of 347 undergraduate students participated in the present study, for a response rate of 87.6%. There were no significant differences in the DES and PSS total scores among students of different grades and sexes. Significant differences were found in the DES "workload" and "self-efficacy beliefs" scores among students from different study years (all P less then 0.05). The Multiple linear regression showed that DES and PSS scores were negatively correlated with GPA, while sex was positively correlated with GPA (all P less then 0.05). Female students had significantly higher GPAs than male students. Conclusions Dental undergraduates in Fujian, China experienced moderate levels of stress. While the amount of stress did not differ by year of study, the sources of stress did differ. Stress scores and sex were negatively correlated with academic performance.Background Heart failure complicated by pulmonary embolism is an extremely rare condition described in the literature. We report a case of very young patient with advanced heart failure against the background of dilated cardiomyopathy of unknown etiology with the presence of blood clots in both ventricles. Case presentation The course of treatment was complicated by acute pulmonary embolism. In emergency setting the patient was qualified for combine surgery pulmonary embolization and implantation of a continuous flow pump as a bridge for heart transplantation. The post-operative course is described in detail as well as reimplantation of the pump due to early thrombosis. Conclusions Performed surgical procedures combined with alteration in anticoagulant drugs was sufficient to stabilize the clinical condition.Background Arthroscopic rotator cuff repair (ARCR) generally yields acceptable clinical results. Hyaluronic acid (HA), a high-molecular-weight polysaccharide, is present in the extracellular matrix of soft connective tissue and synovial fluid, and its injection is known to significantly improve pain and clinical outcomes after rotator cuff injury. Some studies have described the role of HA injections as conservative therapy for rotator cuff tears. Since the subacromial bursa is believed to be the main source of shoulder pain in rotator cuff tears, subacromial injection is frequently used before surgery; however, its relationship with the clinical outcome after surgery remains unclarified. Therefore, we aimed to examine effects of preoperative subacromial HA injection on postoperative clinical outcome in patients with ARCR. Methods Ninety-eight patients were divided into a HA injection group and a non-injection group. The functional outcome measured was the University of California, Los Angeles (UCLA) score. Univariate analysis was performed to obtain variables with p values less than 0.
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